“Fen-Phen� refers to the use of the drugs fenfluramine and phentermine in combination. This combination provided anorectic effects (appetite suppression) and was used for the treatment of obesity. In July of 1997, researchers at the Mayo Clinic and Mayo Foundation reported 24 cases of rare valvular heart disease in women who took the “fen-phen� combination. The FDA had received nine reports of this phenomenon and subsequently received 66 additional reports. Most of these were associated with “fen-phen�, but some involved patients who were taking only fenfluramine, or the related drug, dexfenfluramine. Fenfluramine, manufactured and marketed under the brand name Pondimin by American Home Products Corp., entered the US market in 1973. When used alone, the drug produced only moderate results which were often overshadowed by distressing side effects that included drowsiness and changes in mood. The addition of the stimulant phentermine compensated for those undesirable side effects and produced greater weight loss. In 1992, based upon the results of a study conducted by Michael Weintraub and reported in the Journal of Clinical Pharmacology, physicians began to prescribe this combination “off-label� (it was not approved by the FDA). As the patent on Pondimin (fenfluramine) neared its expiration, Redux (dexfenfluramine), which had already been marketed in Europe, was approved. Dexfenfluramine was manufactured by Interneuron Pharmaceuticals and marketed under the brand name Redux by Wyeth-Ayerst Laboratories, a subsidiary of American Home Products Corp. Based upon reports of valvular heart disease and primary pulmonary hypertension, cases that involved mostly women who had received this combination, the Food and Drug Administration requested that fenfluramine and dexfenfluramine be withdrawn from the market in September of 1997. The FDA did not request that phentermine, the third drug widely used for the treatment of obesity, and the drug used in combination with fenfluramine, be withdrawn. Echocardiograms, which reveal information related to the structure and functioning of heart valves, were abnormal in a much higher than expected number of the patients tested. Approximately 30 percent had abnormal findings, even though they had no symptoms. The abnormalities typically involve the aortic and mitral valves of the heart. The use of fenfluramine leads to weight loss because the drug fosters increased levels of the neurotransmitter serotonin, which is involved with a number of brain functions. In this case, its role is in producing satiety (a feeling of fullness). As of 2004, fen-phen was no longer widely available. In 2005, American Layer magazine reported that more than 50,000 product liability lawsuits had been filed on behalf of people who alleged that they had suffered damages after taking fen-phen. PPH (Primary Pulmonary Hypertension), a disease that thickens the capillaries in the lungs and impairs breathing and for which there is no cure, was linked to derivatives of fenfluramine by the IPPHS (International Primary Pulmonary Hypertension Study.